Cyprus Cardiovascular Disease Educational and Research Trust

Nicosia, Cyprus

Cyprus Cardiovascular Disease Educational and Research Trust

Nicosia, Cyprus
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Holmes M.V.,University College London | Holmes M.V.,University of Pennsylvania | Dale C.E.,London School of Hygiene and Tropical Medicine | Zuccolo L.,University of Bristol | And 170 more authors.
BMJ (Online) | Year: 2014

Objective: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. Design: Mendelian randomisation meta-analysis of 56 epidemiological studies. Participants: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. Main outcome measures: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. Results: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m2). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). Conclusions: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.


Casas J.P.,London School of Hygiene and Tropical Medicine | Casas J.P.,University College London | Ninio E.,French Institute of Health and Medical Research | Panayiotou A.,University of Cyprus | And 26 more authors.
Circulation | Year: 2010

BACKGROUND-: Higher lipoprotein-associated phospholipase A2(Lp-PLA2) activity is associated with increased risk of coronary heart disease (CHD), making Lp-PLA2 a potential therapeutic target. PLA2G7 variants associated with Lp-PLA2 activity could evaluate whether this relationship is causal. METHODS AND RESULTS-: A meta-analysis including a total of 12 studies (5 prospective, 4 case-control, 1 case-only, and 2 cross-sectional studies; n=26 118) was undertaken to examine the association of the following: (1) Lp-PLA2 activity versus cardiovascular biomarkers and risk factors and CHD events (2 prospective studies; n=4884); (2) PLA2G7 single-nucleotide polymorphisms and Lp-PLA2 activity (3 prospective, 2 case-control, 2 cross-sectional studies; up to n=6094); and (3) PLA2G7 single-nucleotide polymorphisms and angiographic coronary artery disease (2 case-control, 1 case-only study; n=4971 cases) and CHD events (5 prospective, 2 case-control studies; n=5523). Lp-PLA2 activity correlated with several CHD risk markers. Hazard ratios for CHD events for the top versus bottom quartile of Lp-PLA2 activity were 1.61 (95% confidence interval, 1.31 to 1.99) and 1.17 (95% confidence interval, 0.91 to 1.51) after adjustment for baseline traits. Of 7 single-nucleotide polymorphisms, rs1051931 (A379V) showed the strongest association with Lp-PLA2 activity, with VV subjects having 7.2% higher activity than AAs. Genotype was not associated with risk markers, angiographic coronary disease (odds ratio, 1.03; 95% confidence interval, 0.80 to 1.32), or CHD events (odds ratio, 0.98; 95% confidence interval, 0.82 to 1.17). CONCLUSIONS-: Unlike Lp-PLA2 activity, PLA2G7 variants associated with modest effects on Lp-PLA2 activity were not associated with cardiovascular risk markers, coronary atheroma, or CHD. Larger association studies, identification of single-nucleotide polymorphisms with larger effects, or randomized trials of specific Lp-PLA2 inhibitors are needed to confirm or refute a contributory role for Lp-PLA2 in CHD. © 2010 American Heart Association, Inc.


Panayiotou A.G.,Cyprus University of Technology | Panayiotou A.G.,Cyprus Cardiovascular Disease Educational and Research Trust | Kamilari E.,University of Cyprus | Griffin M.,Wascular Noninvasive Screening and Diagnostic Center | And 9 more authors.
International Angiology | Year: 2013

Aim: The aim of the study was to test the association between circulating levels of matrix prometalloproteinase1 (pro-MMP1) and its tissue inhibitors TIMP1 and TIMP2 with prevalent cardiovascular events. Methods. Prevalent cardiovascular events were documented in 500 participants of the Cyprus study (46% men) over the age of 40. Serum levels of pro-MMPl, TIMP1 and TIMP2 were measured with ELISA and the association between quartiles of serum levels and presence of cardiovascular disease (CVD) was tested using multivariable binary regression models. Results: Lower serum levels of pro-MMPl and TIMP1 were strongly associated with presence of CVD at baseline even after adjustment for conventional risk factors (Pfor trend=0.006 and P=0.001, respectively) and inflammatory factors (Pfor trend=0.005 and P=0.002, respectively) with people in the highest quartile of pro-MMP1 having a reduced odds for cardiovascular disease by about 70% compared to the lowest quartile (ORadjusted=0.26; 95% CI=0.19 to 0.75; P=0.01), whereas people with TIMP1 levels >11000 ng/mL had a 75% reduced odds for CVD compared to the rest (ORadjusted =0.25; 95% CI=0.11 to 0.60; P for trend=0.002). TIMP2 levels were not associated with prevalent cardiovascular disease. Conclusion. A strong association between lower levels of circulating pro-MMP1 and TIMP1 and risk of prevalent cardiovascular disease in a general population cohort over 40 years is evident, independent from common cardiovascular and inflammatory risk factors. The role of MMP1 and its tissue inhibitors, should be tested further in prospective studies of cardiovascular disease.


Panayiotou A.G.,Cyprus University of Technology | Panayiotou A.G.,Cyprus Cardiovascular Disease Educational and Research Trust | Kouis P.,Cyprus University of Technology | Griffin M.,Cyprus Cardiovascular Disease Educational and Research Trust | And 3 more authors.
International Angiology | Year: 2015

Aim: The aim of this study was to investigate the association between commonly used insulin resistance (IR) indices and the presence and extent of carotid and femoral atherosclerosis in a general population setting. Methods: Cross-sectional analysis of 762 volunteers from the ongoing epidemiological Cyprus Study (46.6% male; mean age=60.5±10.2). 1) Carotid intima-media thickness (IMTcc), 2) carotid and femoral atherosclerotic plaque presence, 3) total plaque area in the carotid/femoral bifurcations (sum of the largest plaques in each carotid/femoral bifurcation-SPAcar/fem), and 4) total plaque area in both carotid and femoral bifurcations (sum of the areas of the largest plaques present in each of the four bifurcations-SPA) were measured using ultrasound at baseline. The HOMA-IR, QUICKI and McAuley indices as well as fasting insulin levels were estimated and their quartiles were used in linear and logistic regression analysis. Results: All IR indices studied were strongly associated with IMTcc (P


Panayiotou A.G.,Cyprus University of Technology | Panayiotou A.G.,Cyprus Cardiovascular Disease Educational and Research Trust | Griffin M.,Vascular Noninvasive Screening and Diagnostic Center | Kouis P.,Cyprus University of Technology | And 7 more authors.
Diabetology and Metabolic Syndrome | Year: 2013

Abstract. Background: We aimed to explore the association between presence and number of components of the Metabolic Syndrome (MetS) and subclinical atherosclerosis outcomes (common carotid intima media thickness, plaque presence and sum of plaque area) in both the carotid and femoral bifurcations. Methods. Cross-sectional analysis of 771 volunteers from the ongoing epidemiological Cyprus Study (46% male; mean age = 60.1 ± 9.8). (a) Carotid intima-media thickness (IMTcc), (b) sum of plaque area in the carotid bifurcations (sum of the largest plaques in each carotid bifurcation-SPAcar), (c) sum of plaque area in the femoral bifurcations (sum of the largest plaques in each femoral bifurcation-SPAfem) and (d) sum of plaque area in both carotid and femoral bifurcations (sum of the areas of the largest plaques present in each of the four bifurcations-SPA) were measured at baseline using ultrasound. Presence and number of components of the MetS was ascertained using the National Cholesterol Education Program ATPIII definition and their association tested using multivariable regression models. Results: MetS was present in 259 (33.6%) individuals and was associated with a 0.02 mm increase in IMTcc (95% CI: 0.00 to 0.04, p = 0.047) after adjustment for age, sex, family history of CVD, alcohol consumption (BU/week) and smoking (pack-years). Each additional component of the MetS was associated with a 16% higher SPA (95% CI: 6.8% to 25.2%, p§ssub§for trend§esub§ = 0.001), a 10% higher SPAcar (95% CI: 5% to 24%, p§ssub§for trend§esub§ = 0.003) and a 14% higher SPAfem in the adjusted model. Conclusions: We confirm an association between the MetS and IMTcc as well as report for the first time an association between the MetS and its components and femoral plaque area, in a general population over 40 years of age. Having any risk factors for the MetS increases the risk for subclinical atherosclerosis, with the risk increasing with each additional component. Using the dichotomous definition of the MetS may be overlooking the risk for subclinical atherosclerosis -and by inference future cardiovascular events- associated with having less than 3 risk factors. © 2013 Panayiotou et al.; licensee BioMed Central Ltd.

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